Improved hemostatic alginic surgical dressings and method of making



Patented Sept. 7, 1954 IMPROVED HEMOSTATIC ALGINIC SURGI- CAL DRESSINGS AND METHOD OF MAK- ING James J. Eberl, Chester, Pa., and William L.

George, Bound Brook, N. J assignors to Johnson & Johnson, a corporation of New Jersey No Drawing. Application March 17, 1950, Serial No. 150,339

9 Claims.

This invention relates to surgical dressings having improved hemostatic properties.

Surgical dressings of the typ used for topical application have long been prepared by securing absorbent material such as cotton gauze to adhesive plaster, such that the gauz can be placed over a wound and the adhesive arranged to hold it in place. More recently the gauze has been treated with antiseptic or antibacterial materials, such as mercurochrome and sulfa drugs.

It has been the ordinary practice to use a bandage to cover a wound to aid the stoppag of bleeding and for the smaller lesions this has usually comprised simply placing a piece of gauze or similar material against the wound and then removing it some time after bleeding has stopped. In this case the only hemostatic agent is in the blood itself. In our co-pendin application, Serial Number 6 10,9538, filed'January 12, 1946, now U. S. Patent No. 2,512,616, of which the present application is a continuation-in-part, we have disclosed an active absorbable hemostatic agent which is capable of stopping bleeding very much faster and which is absorbable in the blood stream and in our co-pending application, Serial Number 71 L174, filed December 5, 1946, now abandoned, of which the present application is a continuation in part, we disclosed an improved surgical dressing which come prises in combination a fibrous material and a water insoluble alginic material.

Alginic acid is a complex organic chemical which can be extracted from certain seaweeds by processes which have long been known. Alginic acid and various alginates eXist in several physical forms including fibers which can be spun into yarns and woven into cloth. It has also been known that alginic acid could be converted or partially converted into various metallic alginates by ejecting a solution of alginic acid into solutions of the appropriate metallic salts and that these metallic alginates can be re-converted into alginic acid without changing their physical form by treatment with hydrochloric acid under controlled conditions. See for example the British patent to Saranson, 21,586, of 1912; the article by Speakman and Chamberlain in the (British) Journal of the Society of Dyers and Colorists, October 1944, page 264; and the article by Chamberlain, Johnson, and Speakman in the same journal, January 1945, page 137.

We show in our earlier applications that alginic acid in the gel, granular and fibrous forms has the property of coagulating blood and thus stopping bleeding when pressed into contact with wounds. The cause of this hemostatic action and the mechanism by which it takes place is not completely understood, but it is believed that the hemoglobin. of the blood when in contact with the alginic acid froms a complex which may be either a fibrous mass or a gelatinous or sticky structure, and that when this structure is formed in contact with the surface of a wound, it mechanically prevents the flow of blood from the wound. Whatever the action, we have discovered that when alginic acid is pressed into contact with a wound, even one which is profusely bleeding due to severed arteries, the bleeding is stopped readily and the alginic acid can be cleanly removed leaving a clean red surface. The hemostatic action is quite fast and the material is much cheaper and easier to use than known hemostatic agents.

This invention is based on the surprising discovery that the hemostatic action of alginic acid dressings may be materially accelerated and substantially enhanced by addition to th alginic acid or alginate salt of from one-half to ten per cent by weight of another acid. The preferred acid is nitric acid, although good results may be obtained using one or more of the other mineral and organic acids. For the sake of clarity, in the specification and claims, the expression alginate material has been employed to include algin c acid, metal salts of alginic acid, and alginic acid-metal alginate complexes. Also for the sake of clarity, in the claim, the expression admixture is employed in the sense of physical interminglin (to distinguish from chemical combination) and is intended to include such intermingling resulting from coating by solutions as well as literal mixing.

The acid may be mixed into the alginate material, or, in preferred forms of the invention, the alginate material or alginate coated material may be passed through a dilute solution of the acid, preferably a five to ten percent solution thereof. In either case the non-alginic acid content of the alginate material is best checked by titration after completion of the treatment.

The following table shows a list of alginic acid or alginate salt compositions which proved at least twice as effective in hemostasis as the corresponding pure alginic materials using representative non-alginic acids:

N 0n-Algiuic Acid Used in Alginic Acid Compositions and Also Used in Cal- Perceut of N on-Alginic cium Alginate Compositions Acid Used:

Citric 1-10 (5% preferred). Maleic 1-10 (6% preferred). Malic 1 10 (5% preferred). Nitric l-3 (2% preferred). Phosphor 0.5-2 (1% preferred). Tartaric 1-10 (5% preferred).

3 by at least twenty-five per cent. In the case of the salts the action of the acids is much more pronounced and produces pronounced hemostasis even in cases where the alginate salt (for instance calcium alginate) itself produces little hemostasis.

The preferred alginates are those of the type disclosed in our co-pending application, Serial No. 640,988, filed January 12, 1946. This application discloses alginic materials best suited for the steam sterilization commonly applied to surgical dressings.

Example I For instance it shows that auze woven from calcium alginate is washed with dilute hydrochloric acid, of pH about 1.6 until the desired proportion of conversion to alginic acid has occurred, after which the gauze is washed in water to remove the acid. Thereafter the gauze is buffered to a pH' of about 4 to stabilize the unconverted portion of the alginic acid, and dried. The buffering may be accomplished by dipping in potassium acid phthalate and then washing. This results in a long chain molecule in which calcium has replaced the hydrogen ion in some of the carboxyl groups and. potassium has replaced the hydrogen ion in other carboxyl groups. This complex is insoluble in water, there being insufiicient potassium present in the molecule to produce solubility. The result is a gauze which has not changed its physical form or absorbency, but is composed of the material described above, a combination of alginic acid and calcium alginate.

We have found that the proportion of conversion depends on the concentration of the acid. Equilibrium of the conversion appears to occur in about five minutes. The amount of proportion of conversion is determined by measuring the calcium content of the converted product. Pure calcium alginate contains about 10.38% calcium. We have found that when the calcium content of the converted alginic acid-alginate combination is greater than about 6%, the hemostatic action of the material is undesirably slow. The hemostatic quality increases with decreasing calcium content, until at zero calcium content, or pure alginic acid, the hemostatic action is greatest. However, material having a calcium content below about 2% begins to lose strength in a steam sterilizer, and materials with calcium contents materially below this are degraded, weak and easily friable after such treatment. Accordingly we prefer to immerse the calcium alginate gauze in hydrochloric acid for a time suflicient to give a calcium content between about 2% and about 6%, and even between about 3% and about 4.5%, since the hemostatic quality of the material having a calcium content higher than 4.5% may not be adequate for some uses.

Thus when the surgical dressings accordin to our invention are to be sterilized by methods other than exposure to steam, we may use either pure alginic acid, or alginic acid which has been only slightly converted into an alginate (for example, containing about 2% calcium). This is preferably buffered to a pH of about 4 to stabilize the material. But when steam sterilizable dressings are required, we prefer to form them of alginic acid-alginate combination which contains sufficient metal to stabilize the material to exposure to steam.

This product works particularly well when treated in accordance with the preferred form of the phosphoric acid example of the table, and hemostasis is then accelerated by at least fifty per cent.

In another form of the invention alginate materials may be coated onto the surface of an absorbent base, such as gauze. An antibacterial material may or may not be used with the alginate coating, depending upon the particular purpose of the product and its proposed manner of use. A typical example of such a coating is disclosed in our co-pending application, Serial No. 714,174, filed December 5, 1946:

Example II 0.7570 part of tyrothricin was mixed with 40 parts of propylene glycol and parts of water. A mechanical agitator was used to get the tyrothricin in solution. Separately 50 parts of alginic acid was dissolved in 412 parts of water by the addition of 18 parts of 28% ammonium hydroxide. After all the alginic acid was in solution, it was filtered through a gauze filter to take out any siliceous impurities. To this solution was added 20 parts of tyrothricin solution prepared above. The combined solution was allowed to stand for several hours and then a strip of cotton gauze was immersed in the combined solution for a few minutes, put through a squeeze roller, and dried in an oven at 70 C. After drying, the gauze was again immersed in the combined solution, squeezed, and dried a second, third and fourth time, until the material picked up by the gauze constituted 61.2 per cent by weight on a dry basis of the total material.

A small strip of the gauze thus treated was then secured to a strip of adhesive tape and two layers of untreated gauze placed between the outer layer of treated gauze and the adhesive tape backing. This bandage was placed upon a bleeding surface out and found to give excellent hemostatic results.

This product works particularly well when treated in accordance with the preferred form of the nitric acid example of the table, and hemostasis is then accelerated by at least fifty per cent.

Substantial improvement and acceleration of hemostasis results from addition to the alginate materials of the above examples of amounts of any acid in accordance with the invention, and particularly of the amounts and types of acid of the table shown earlier in this specification.

The invention is, however, not limited to the examples shown herein, but is broad and many modifications, obvious to those skilled in the art. are included within its spirit.

What is claimed is:

l. The method of making a surgical dressing having improved stability and hemostatic prop erties which comprises adding to a surgical dressing containing alginate material, a minor amount, between about 0.5% and about 10% by weight dry basis, based on said alginate material, of an acid of the group consisting of citric, maleic, malic, nitric, phosphoric and tartaric acids in solution, the amount of said acid being in excess of that required to convert the alginate material to alginate salt content below a value corresponding with 3.0% calcium, and thereafter drying said dressing without removing unreacted acid nor reaction products.

2. The method according to claim 1 wherein the solution is an aqueous solution.

3. The method according to claim 1 wherein said acid comprises nitric acid.

4. The method according to claim 1 wherein said acid comprises phosphoric acid.

5. A surgical dressing having improved stability and hemostatic activity prepared by adding to a surgical dressing containing alginate material, a minor amount, between about 0.5% and about 10% by weight dry basis, based on said alginate material of an acid of the group consisting of citric, maleic, malic, nitric, phosphoric and tartaric acids in solution, the amount of said acid being in excess of that required to convert the alginate material to alginate salt content below a value corresponding with 3.0% calcium, and thereafter drying said dressing without removing unreacted acid nor reaction products.

6. A surgical dressing according to claim 5 wherein the alginate material is present in fibrous form.

7. A surgical dressing according to claim 5 20 9. A surgical dressing according to claim 5 wherein said acid comprises phosphoric acid.

References Cited in the file of this patent UNITED STATES PATENTS Number Name Date 2,512,616 Eberl et a1 June 2'7, 1950 FOREIGN PATENTS Number Country Date 116,134 Australia Nov. 26, 1942 OTHER REFERENCES Annals O'tol. and Laryngology, September 1943, page 553.

American Druggist, November 1945, page 45.

J. Amer. Pharm. Assoc., Scientific Ed., May 1946, page 145.

Trans. Amer. Acad. Ophthalmology and Laryngology, August 1943, page 433.

\ Science, May 17, 1946, page 634.

Fairbairn et al.: Absorbable Haemostatics, The Pharmaceutical Journal, February 28, 1948, pages 149, 150. 

1. THE METHOD OF MAKING A SURGICAL DRESSING HAVING IMPROVED STABILITY AND HEMOSTATIC PROPERTIES WHICH COMPRISES ADDING TO A SURGICAL DRESSING CONTAINING ALGINATE MATERIAL, A MINOR AMOUNT, BETWEEN ABOUT 0.5% AND ABOUT 10% BY WEIGHT DRY BASIS, BASED ON SAID ALGINATE MATERIAL, OF AN ACID OF THE GROUP CONSISTING OF CITRIC, MALEIC, MALIC, NITRIC, PHOSPHORIC AND TARTARIC ACIDS IN SOLUTION, THE AMOUNT OF SAID ACID BEING IN EXCESS OF THAT REQUIRED TO CONVERT THE ALGINATE MATERIAL TO ALGINATE SALT CONTENT BELOW A VALUE CORRESPONDING WITH 3.0% CALCIUM, AND THEREAFTER DRYING SAID DRESSING WITHOUT REMOVING UNREACTED ACID NOR REACTION PRODUCTS. 